Suchttherapie 2013; 14 - PL_3
DOI: 10.1055/s-0033-1351398

Neurocircuitry of Addiction: A brain reward deficit, stress surfeit and executive function disorder

G Koob 1
  • 1The Scripps Research Institute, La Jolla

Drug addiction has been hypothesized to be a chronically relapsing disorder of compulsive drug seeking and taking that progresses through three stages: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Drug addiction includes elements of positive reinforcement (binge/intoxication stage) and negative reinforcement (withdrawal/negative affect stage). The construct of negative reinforcement in addiction is defined as drug taking that alleviates a negative emotional state.

The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain stress systems within the ventral striatum, extended amygdala, and frontal cortex that make addiction a reward deficit, stress surfeit, executive function disorder.

Acute withdrawal from all major drugs of abuse increases reward thresholds, increases anxiety-like responses, and increases the activity of brain CRF and dynorphin systems in the ventral striatum, extended amygdala and the frontal cortex. CRF receptor antagonists block anxiety-like responses associated with withdrawal, the increases in reward thresholds produced by withdrawal from drugs of abuse, and compulsive-like drug taking during extended access. Increases in CRF in the frontal cortex are linked to deficits in executive function that also may facilitate the transition to compulsive-like responding. Excessive drug taking also engages activation of dynorphin in the ventral striatum, extended amygdala and medial prefrontal cortex that contributes to compulsive-like drug taking.

Brain stress response systems are activated by acute excessive drug intake, sensitized during repeated withdrawal, persist into protracted abstinence, and contribute to the development and persistence of addiction. A role of the brain stress systems in addiction not only provides insight into the neurobiology of the dark side of addiction but also provides novel targets for the treatment of addiction.